Elevated preoperative suPAR is a strong and independent risk marker for postoperative complications in patients undergoing major noncardiac surgery (SPARSE)

Chalkias, Athanasios; Laou, Eleni; Kolonia, Konstantina; Ragias, Dimitrios; Angelopoulou, Zacharoula; Mitsiouli, Eleni; Kallemose, Thomas; Smith-Hansen, Lars; Eugen‐Olsen, Jesper; Αrnaoutoglou, Eleni

doi:10.1016/j.surg.2021.10.012

Cited by 12 publications

(23 citation statements)

References 37 publications

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“…It is an immune mediator involved in numerous physiological and pathological pathways and its levels in circulation reflect the ability of the patient to cope with diseases. 16 , 17 An increase in suPAR levels can be triggered by various stimuli, including SARS‐CoV‐2, and suPAR is highly expressed in lung tissue, 18 which may be critical for disease progression. Indeed, suPAR has been recently implicated in the evolution of COVID‐19 and its associated complications 12 , 19 , 20 and represents the inflammatory biomarker that is most reflective of the hyperinflammatory state in patients with comorbidities.…”

Section: Discussionmentioning

confidence: 99%

“…It is worthy of note that suPAR is not an acute phase reactant, has no circadian variation, and remains stable during episodes of acute stress. 3 , 8 , 17 Based on the specific characteristics of suPAR and the other markers, a multi‐level approach using key clinical and laboratory data could improve prediction at hospital admission. 27 Thus, we constructed the SALGA model that can best estimate the WHO‐CPS score.…”

Section: Discussionmentioning

confidence: 99%

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Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Papagiannakis

Tourlakopoulos

Pagonis

et al. 2022

Eur J Clin Investigation

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Background COVID‐19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID‐19. Methods The primary outcome measure in this international, multi‐centre, prospective, observational study with adult patients hospitalized primarily for COVID‐19 was the association of WHO Clinical Progression Scale (WHO‐CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin‐6. Admission plasma suPAR levels were determined using the suPARnostic ® ELISA and suPARnostic ® Turbilatex assays. Results Seven hundred and sixty‐seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log‐suPAR levels significantly correlated with WHO‐CPS score, with each doubling of suPAR increasing the score by one point ( p < .001). All the other markers were also correlated with WHO‐CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47–3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO‐CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759–0.836). Conclusions suPAR levels significantly correlated with WHO‐CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Papagiannakis

Tourlakopoulos

Pagonis

et al. 2022

Eur J Clin Investigation

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“…We considered suPAR levels higher than 5.5 ng mL −1 as a clinically important indicator of systemic inflammation, as previously suggested [ 32 ]. A second cut-off at 10 ng mL −1 was chosen to indicate especially high suPAR levels [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Healthy individuals can also be genetically predisposed to higher or lower suPAR levels, which gives suPAR a potential prognostic value in associated diseases [ 6 ]. Of note, mounting evidence from studies including cancer and non-cancer patients suggests that suPAR can serve as an independent predictor of postoperative complications and outcomes compared to other biomarkers [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. This could be explained in part by the stability of suPAR, which is significantly higher than that of other markers (e.g., C-reactive protein (CRP) or proinflammatory cytokines) and remains unaffected by general anesthesia and operative trauma [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Preoperative Basal Inflammatory State, Measured by Plasma suPAR Levels, with Intraoperative Sublingual Microvascular Perfusion in Patients Undergoing Major Non-Cardiac Surgery

Chalkias

Papagiannakis

Saugel

et al. 2022

JCM

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It remains unknown whether chronic systemic inflammation is associated with impaired microvascular perfusion during surgery. We evaluated the association between the preoperative basal inflammatory state, measured by plasma soluble urokinase-type plasminogen activator receptor (suPAR) levels, and intraoperative sublingual microcirculatory variables in patients undergoing major non-cardiac surgery. Plasma suPAR levels were determined in 100 non-cardiac surgery patients using the suPARnostic® quick triage lateral flow assay. We assessed sublingual microcirculation before surgical incision and every 30 min during surgery using Sidestream Darkfield (SDF+) imaging and determined the De Backer score, the Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Elevated suPAR levels were associated with lower intraoperative De Backer score, Consensus PPV, and Consensus PPV (small). For each ng mL−1 increase in suPAR, De Backer score, Consensus PPV, and Consensus PPV (small) decreased by 0.7 mm−1, 2.5%, and 2.8%, respectively, compared to baseline. In contrast, CRP was not significantly correlated with De Backer score (r = −0.034, p = 0.36), Consensus PPV (r = −0.014, p = 0.72) or Consensus PPV Small (r = −0.037, p = 0.32). Postoperative De Backer score did not change significantly from baseline (5.95 ± 3.21 vs. 5.89 ± 3.36, p = 0.404), while postoperative Consensus PPV (83.49 ± 11.5 vs. 81.15 ± 11.8, p < 0.001) and Consensus PPV (small) (80.87 ± 13.4 vs. 78.72 ± 13, p < 0.001) decreased significantly from baseline. In conclusion, elevated preoperative suPAR levels were associated with intraoperative impairment of sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery.

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“…The underlying study was conducted in accordance with Good Clinical Practice guidelines, the principles of the Declaration of Helsinki, and relevant regulatory requirements. The original study was registered in ClinicalTrials.gov (NCT03851965, February 22, 2019) [10]. The UHL Institutional Review Board approved the study (IRB no.…”

Section: Methodsmentioning

confidence: 99%

Association of effective circulating blood volume with sublingual RBC velocity and microvessel pressure difference in anesthetized individuals: A clinical investigation and computational fluid dynamics modeling

Chalkias

Xenos

2022

Preprint

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BackgroundAlthough changes in effective circulatory volume may affect microcirculatory red blood cell (RBC) velocity and oxygen extraction ratio, no systemic variable has been consistently associated with hemodynamic coherence. We therefore evaluated the association between mean circulatory filling pressure and microcirculatory perfusion and oxygenation.MethodsThis analysis included anesthetized individuals in steady-state physiology. We assessed the correlation of mean circulatory filling pressure analogue (Pmca) with sublingual microcirculation and RBC velocity using SDF+ imaging and a modified optical flow-based algorithm. We also reconstructed the 2D microvessels and applied Computational Fluid Dynamics (CFD) to evaluate the correlation of Pmca and RBC velocity with the obtained pressure and velocity fields in microvessels from CFD [pressure difference (Δp)].ResultsTwenty adults were included in the study, of whom 12 (60%) were men and 8 (40%) were women, with a median age of 39.5 years (IQR 35.5-44.5). Sublingual velocity distributions were similar and followed a log-normal distribution. A constant Pmca value of 14 mmHg was observed in all individuals with sublingual RBC velocity of 6-24 μm sec-1, while a Pmca <14 mmHg was observed in those with RBC velocity >24 μm s-1. When Pmca ranged between 11 mmHg and 15 mmHg, Δp fluctuated between 0.02 Pa and 0.1 Pa.ConclusionsThese data suggest that the intact regulatory mechanisms may maintain a physiological coupling between systemic hemodynamics and tissue perfusion and oxygenation when Pmca is 14 mmHg.HIGHLIGHTSChanges in effective circulatory volume may affect microcirculatory red blood cell (RBC) velocity and oxygen extraction ratio, but no systemic variable has been consistently associated with hemodynamic coherenceWe found that a mean circulatory filling pressure analogue (Pmca) value of 14 mmHg maintains sublingual RBC velocity at 6-24 μm s-1A Pmca <14 mmHg is observed in individuals with RBC velocity >24 μm s-1Microvessel pressure difference is maintained constant when Pmca ranges between 11 mmHg and 15 mmHgThese findings imply that tissue oxygenation can be maintained in very low RBC velocitiesTherapeutic strategies and translational research beyond optimizing macrohemodynamics and microcirculatory flow are required, including normalizing red blood cell velocityBRIEF COMMENTARYBackgroundHemodynamic coherence is not well-investigated and no systemic hemodynamic variable has been consistently correlated with microcirculatory perfusion and tissue oxygenation.Translational SignificanceThe present study provides a novel method to monitor hemodynamic coherence and tissue perfusion, which can aid in the identification of novel hemodynamic phenotypes and enhance microcirculation-guided therapeutic strategies, optimizing local delivery of oxygen. Our findings also imply that (1) tissue oxygenation can be maintained in very low red blood cell velocities; and (2) therapeutic strategies and translational research beyond optimizing macrohemodynamics and microcirculatory flow are required, including normalizing red blood cell velocity.

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Elevated preoperative suPAR is a strong and independent risk marker for postoperative complications in patients undergoing major noncardiac surgery (SPARSE)

Cited by 12 publications

References 37 publications

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Circulating suPAR associates with severity and in‐hospital progression of COVID‐19

Association of Preoperative Basal Inflammatory State, Measured by Plasma suPAR Levels, with Intraoperative Sublingual Microvascular Perfusion in Patients Undergoing Major Non-Cardiac Surgery

Association of effective circulating blood volume with sublingual RBC velocity and microvessel pressure difference in anesthetized individuals: A clinical investigation and computational fluid dynamics modeling

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